Outer layer having entanglement of hydrophobic polymer host and hydrophilic polymer guest

ABSTRACT

An outer layer having an entanglement comprising an intermingling of cloaked hydrophilic guest and a hydrophobic polymer host, wherein molecules of the guest have been crosslinked with each other. Under certain circumstances, using complexes of the guest may be desirable or even necessary. The intermingling of the guest and host includes a physical tangling, whether it also comprises crosslinking by primary bonding (e.g., chemical/covalent bonding) there-between. Also a method of producing an outer layer having such an entanglement, including the steps of: temporarily cloaking at least a portion of the hydrophilic groups of the guest; intermingling at least a portion of the cloaked groups with a porous polymeric structure by diffusing the guest with cloaked groups into at least a portion of the structure&#39;s pores; within the pores, crosslinking at least a portion of the molecules of the guest with the guest; and removing the cloaking. Cloaking may be performed by silylation or acylation. Intermingling may be performed by producing a mixture of guest and host (whether in solution, powdered, granular, etc., form); next, a crosslinking of the guest with itself is performed; then, the mixture is molded into the outer layer.

This application claims priority to pending U.S. provisional patentapplication serial no. 60/340,777 filed on behalf of the assignee hereofon 29 Oct. 2001.

The invention disclosed herein was made in-part with United Statesgovernment support awarded by the following agency: National ScienceFoundation, under contract number BES-9623920. Accordingly, the U.S.Government has rights in this invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

In general, the present invention relates to the synthesis and use ofinterpenetrating polymer networks (IPN), or other crosslinkedmulti-polymer mixtures, in connection with medical devices such astemporary and permanent implants, surgery instruments and aids, andother mechanisms that have a member or component with an outer surfaceexposed to the frictional wear of load bearing, or to any H₂Oenvironment (gas, liquid, or solid/ice-crystals) where lubricity oroptical clarity is a consideration.

Of interest, here, is the synthesis of a novel outer layer having anentanglement of at least a hydrophobic polymer host and a hydrophilicguest, wherein molecules of the guest are crosslinked through primarybonding (e.g., chemical/covalent cross-linking). The unique layer, asfabricated, has a generally hydrophilic outer surface useful in a widevariety of applications when laminated, thermally or otherwise bonded,formed, or integrated with a base member or structure comprising ahydrophobic polymer. The outer layer may be incorporated into acomponent, piece, module, feature, or any structure/member to produce a‘system’ such that the hydrophilic outer surface provided is interior-or exterior-facing, etc. A non-exhaustive list of possibilitiescontemplated hereby for the generally hydrophilic outer surface producedatop the novel outer layer, include: a bearing surface (for variousitems such as gears, fishing rod eyelets, bearings of all types, jointand other weight-bearing mechanisms, whether incorporated as part ofmanufacturing equipment, as part of the manufactured product itself,etc.); a flexible barrier surface separating a first and second area(such flexible barriers to include the membrane material or tubing usedfor catheter balloons, catheter tubing, hot air balloons, condoms, IVtubing, diaphragms, flexible bladders, etc.); a transparent membersurface (such members to include the transparent planar or curvedpolymeric films and sheet material used where optical clarity is soughtsuch as for fish tanks, polymeric covers for vehicle, water- or aircrafthead-lamps and blinkers/fog-lights, covers for spot-lights, windows onor in a vehicle, aircraft, watercraft, and spacecraft, monitor andtelevision screens, ophthalmic lenses, camera lenses and view-finders,etc.); an in vivo implant surface (any of a variety of total or partialjoint replacements, splints, stents, diaphragms, etc.); a drag reductionsurface (for components of a vehicle, watercraft, aircraft andspacecraft such as hulls, pontoons, vehicle-body parts, blades/runners,etc., as well as the glide-surface of snowboards, water and snow skis,and so on); a reaction resin surface (such as research or industrial usecomponents); a topical dressing surface (such dressings to include,without limitation, those used for medical/veterinary applications suchas adhesive bandages, sterile pads for wounds and surgical procedures,bandage tape/adhesive, ace bandages, soft casts, etc.); and a dentalsplint surface (such splints to include mouth-guards,tooth/jaw-correction splints, etc.).

Although bio-compatible hearing surfaces are of noteworthy focus, here,due to their importance in reconstructive orthopedic and plasticsurgical procedures, many applications require bearing surfaces ofenhanced lubricity and structural integrity capable of withstandingprolonged, continuous mechanical wear and stresses used under many typesof conditions and environments (such as equipment having bearingstructures submersed for operation in aqueous environments or used toprepare food, medicines, and other items for consumption or ingesting).In the spirit and scope of design goals contemplated hereby, the novelouter layer having an entanglement can be produced according to theinvention using many hydrophobic polymer hosts, including ultra highmolecular weight polyethylene (UHMWPE), acrylics, nylons,polytetra-fluoroethylene (TEFLON®), and other olefins—andmore-generally, any hydrocarbon-based polymer generally considered“water-insoluble” (i.e., hydrophobic to a high degree)—as well as thepolymeric materials used for items identified above (namely, bearingstructures, flexible barriers, transparent members, implants, wounddressings, dental splints, and so on) may be used; also, a wide varietyof hydrophilic guests may be used in an outer layer according to theinvention, including without limitation: polyions and non-ionichydrophilic polymers, and more specifically, polysaccharides (e.g., theglycosaminoglycan, hyaluronic acid), salts of glycosaminoglycans,nucleic acids, polyvinylpyrrolidones, peptides, polypeptides, aminoacids (e.g., poly-L-lysine, PLL), proteins, lipoproteins, polyamides,polyamines, polyhydroxy polymers, polycarboxy polymers, phosphorylatedderivatives of carbohydrates, sulfonated derivatives of carbohydrates,interleukin-2, interferon, and phosphorothioate oligomers.

In one aspect, by way of example, the instant invention is directed to abearing structure comprising an outer layer having an entanglement of anUHMWPE hydrophobic host and a hydrophilic polymer guest (such ashyaluronic acid, HA, or other polyion) produced by, first, diffusing thehydrophilic guest (HA) into the hydrophobic host (UHMWPE) whereby thehydrophilic guest is temporarily made sufficiently hydrophobic togenerally prevent phase separation thereof until being cross-linked,thus creating an IPN. This IPN is effective as a bio-compatible bearingsurface, exhibiting ‘dry’ lubricity. An outer layer/IPN produced in thismanner has unique characteristics; the guest diffuses into the surfaceof the host creating a diffusion profile extending a depth, d, from thebearing outer surface, throughout which a concentration gradient ofcross-linked guest entangled within polymer host is created. Principlesof classical mechanics provide some guidance regarding the diffusionprofile: Fick's laws predict, under selected circumstances, that therate of diffusion of matter across a plane is proportional to thenegative of the rate of change of the concentration of the diffusingsubstance in the direction perpendicular to the plane. The diffusionprofile of the IPN may resemble that of a Boltzman distribution, aconcept that incorporates an exponential distribution and istraditionally used in connection with statistical mechanics and appliedwhere the molecules of interest obey laws of classical mechanics.

By way of background, lubricious coatings and surface graftings topolymeric structures have been designed by others for other purposes.For example, Halpern et al, U.S. Pat. No. 4,959,074 uses one or more(with intermediate drying periods) polysaccharide coatings applied to aPlexiglas panel from water solution, by conventionalmechanically-superficial methods such as spraying, knife-coating,brushing, or dipping a coat-thickness that “will depend upon themolecular weight and viscosity of the polysaccharide”. Halpern et al.explains that its polysaccharide coating is for plastics used inspectacle lenses, contact lenses, and aircraft windshields (all of whichtend to use have high flexural modulus capable of being shaped intoforms that are water-insoluble and hydrophobic to a high degree). Giustiet al. U.S. Pat. No. 5,644,049 describes an interpenetrating polymernetwork (IPN) biomaterial in the form of very soft structures (a film,membrane, a sponge, a hydrogel, a guide channel, a thread, a gauze, ornon-woven tissue), wherein one of the polymer components is an acidicpolysaccharide or a semi-synthetic derivative thereof. Cross-linking orgrafting is done by using compounds capable of generating radicals, orvia functional groups on the acidic polysaccharide and the syntheticpolymer. One can appreciate that as coatings and graftings designed forpurposes other than bearing weight, none of the known coatings andsurface graftings will withstand the severe, repetitive mechanicalstresses to which artificial joint surfaces are subject, for any lengthof time. Each falls short of producing a bio-compatible surface ofsufficient surface lubricity and structural integrity capable ofwithstanding the wear and stress to which of bearing structures areexposed, especially implanted structures.

In earlier work of the applicants to synthesize an IPN using apoly-L-lysine (PLL) guest compound in a salt form, PLL-HBr, the narrowfocus was to use PLL-HBr to create an IPN capable of attractingproteoglycans in synovial joint fluid for lowering the friction and wearof UHMWPE. For reference, see: Beauregard, Guy P., James, Susan P.,“Synthesis and Characterization of Novel UHMWPE Interpenetrating PolymerNetwork” Biomedical Sciences Instrumentation, vol. 35, InstrumentSociety of America, Research Triangle Park, N.C., 1999, also presentedat the 36th Annual Rocky Mountain Bioengineering Symposium, CopperMountain, Colo., Apr. 16-18, 1999.

In this previous work, applicants demonstrated the synthesis of asequential IPN using UHMWPE as the host polymer and poly-L-lysine (PLL)as the guest polymer. According to their previous work, the sequentialIPN synthesized using PLL as the guest polymer in a UHMWPE host did notmeet all targeted expectations. Steps associated with using a PLL guestemploying silylation, include:

(1) Silylation of PLL-HBr to PLL-SiMe₃

The HBr salt of PLL (PLL-HBr) is replaced with the much less polartrimethylsilyl (SiMe₃) group.

(2) Swelling PLL-SiMe₃ into the UHMWPE Host Network

Samples of UHMWPE were placed in a solution of a 2.5% (w/v) PLL-SiMe₃and xylenes based on the original PLL-HBr starting weight. As the UHMWPEswells in the presence of the xylenes, the PLL-SiMe₃ diffuses into thehost UHMWPE network.

(3) Crosslinking of the PLL-SiMe₃ in situ

To terminate the diffusion, the swelling solution was removed and asolution of small molecular weight crosslinkers in xylenes wasintroduced. The crosslinkers diffused into the swollen UHMWPE where theycrosslinked the PLL-SiMe₃ in situ. The contents of the reaction vesselwere rinsed with xylenes.

(4) Drying of the IPN The crosslinked IPN was deswollen and dried undervacuum.

(5) Hydrolysis of the IPN

The un-crosslinked trimethylsilylated sites on the PLL are returned totheir cationic nature upon contact with water.

The surfaces produced indicated undesirable increase of surfaceroughness and the coefficient of friction. At synthesis conditions lessextreme than those used by the authors, not enough PLL is resident inthe UHMWPE surface to recruit sufficient native polar or ionic moietiesto reduce the coefficient of friction. Therefore, a new and effectiveIPN system is needed; and accordingly, the invention details use of anHA guest to create a novel IPN.

One can readily appreciate the improvements made by the applicants tothis earlier, circa 1999, work: In an intervening work, fullyincorporated into applicants' co-pending provisional patent application(identified above, to which applicants claim priority), and incorporatedherein by reference (labeled here, as well as in the provisionalapplication, as ATTACHMENT A) applicants provide technical backgroundinformation and details of experimental techniques and rigorousengineering analysis employed in connection with producing their uniqueouter surface, method of producing the outer surface, and associatedsystem of the invention disclosed here. While representativeimplementations have been showcased here, the outer surface has a widevariety of applications as contemplated.

SUMMARY OF THE INVENTION

It is an object to produce an outer layer comprising an entanglement ofa hydrophilic guest, at least a portion of which is crosslinked amongitself, and a hydrophobic polymer host. The layer has a generallyhydrophilic outer surface; it can be structurally incorporated, such asby way of lamination, adhesion, bonding using pressure and thermalenergy, or otherwise interlinked with polymeric networks/structures of asubstantially hydrophobic nature to create a system having a high amountof structural integrity. The layer can be synthesized as an integralstep of the process to fabricate the system, or synthesized ahead oftime and incorporated into a base structure, or built to a thickness,size/shape to operate independently in a selected application.

Briefly described, once again, the invention includes an outer layerhaving an entanglement comprising an intermingling of cloakedhydrophilic guest and a hydrophobic polymer host, wherein molecules ofthe guest have been crosslinked with each other. The hydrophilic guestof the entanglement may comprise a compound selected from a specifiedgroup consisting of polyions, polysaccharides (including theglycosaminoglycan, hyaluronic acid), salts of glycosaminoglycans,nucleic acids, polyvinylpyrrolidones, peptides, polypeptides, proteins,lipoproteins, polyamides, polyamines, polyhydroxy polymers, polycarboxypolymers, phosphorylated derivatives of carbohydrates, sulfonatedderivatives of carbohydrates, interleukin-2, interferon, andphosphorothioate oligomers, with-or-without amino acids, as well asother hydrophilic polymers. As further identified: polyhydroxy polymersinclude, among others, polyvinyl alcohol and polyethylene glycol; andpolycarboxy polymers include, among others, carboxymethylcellulose,alginic acid, sodium alginate, and calcium alginate.

The intermingling of the guest and host includes a physical tangling,whether it also comprises crosslinking by primary bonding(chemical/covalent bonding) therebetween. Depending upon the type ofintermingling employed, the guest selected for intermingling with thehost, the type of crosslinking of the guest (by chemical crosslinking orby way of thermal, ultra-violet “UV”, or other suitable energy source),as well as composition and form of the host (e.g., fully- orpartially-consolidated porous structure, in powdered form, in solution,and so on), cloaking may be by any way suitable, such as by way ofperforming silylation or acylation, of the guest—making it morehydrophobic. Under certain circumstances, using complexes of the guestmay be desirable or even necessary—especially where the guest is notsufficiently hydrophobic to undergo the selected cloaking technique. Thecloaked groups are then returned to an initial hydrophilic state toproduce a generally hydrophilic outer surface of the layer, this can beby performing a hydrolysis reaction.

In the event hyaluronic acid is selected as the guest, intermingling maybe done with complexes thereof represented according to the expressionHA⁻- QN⁺, where HA represents hyaluronic acid and QN⁺ represents aparaffin ammonium cation. QN⁺ may be selected from the followingnon-exhaustive group of cations including: alkyltrimethylammoniumchloride, alkylamine hydrochloride, alkylpyridinium chloride, andalkyldimethylbenzyl ammonium chloride (using chloride salts), andalkyltrimethylammonium bromide, alkylamine hydrobromide, alkylpyridiniumbromide, and alkyldimethylbenzyl ammonium bromide (using bromide salts).If cloaking is performed by silylation of the guest (or of guestcomplexes) using a silylating agent in suitable solvent, the cloakedhydrophilic groups that result comprise silylated functional groups.Cloaking of the hydrophilic groups of the guest done by acylationresults in acylated functional groups. The QN⁺ groups may be dissociatedfrom said guest complexes in, for example, a suitable salt solution.

In the event the host comprises a porous polymeric structure, a portionof the crosslinked molecules of the guest is preferably located within aplurality of pores of this porous host structure. This can be done bydiffusion into at least a portion of the pores of the host structureprior to crosslinking of guest molecules therewithin. Prior to diffusionof guest complexes into the host (whether the host is a porousstructure), the host may be swollen in a solution comprising guestcomplexes for a length of time—this being done to aid in thediffusion-mechanics of intermingling host with guest. Guest complexesare preferably returned to a pre-complex state by dissociation of the‘complex’ group therefrom. In the event the intermingling is done withthe cloaked guest in powdered form (by, for example, vacuuming dryingwashed acylated guest) and the host in powdered form, once the cloakedgroups have been returned to an initial hydrophilic state, the outerlayer may be produced by way of a thermal molding of the powdered formof the guest with the host. In the case where a powered mixture ofcloaked guest and host has been produced, it may be preferable to cloakby performing acylation resulting in acylated functional groups on theguest; these acylated functional groups are preferably, later, returnedto an initial hydrophilic state to produce the generally hydrophilicouter surface of the layer.

A system including the outer layer can be formed into a structurecomprising a base that comprises host hydrophobic polymer material. Thegenerally hydrophilic outer surface of the layer may be any of a widevariety of surfaces, including those listed: a bearing surface; aflexible barrier surface separating a first and second area; atransparent member surface; an in vivo implant surface; a drag reductionsurface; a reaction resin surface; a topical dressing surface; and adental splint surface.

In another characterization, the invention includes a method ofproducing an outer layer having an entanglement comprising a hydrophobicporous polymeric structure and a hydrophilic guest. This method has thesteps of: temporarily cloaking at least a portion of the hydrophilicgroups of the guest; intermingling at least a portion of the cloakedguest with the porous polymeric structure by diffusing the cloaked guestinto at least a portion of the structure's pores; within the pores,crosslinking at least a portion of the molecules of the guest with theguest; and then removing the cloaking to produce a generally hydrophilicouter surface of the outer layer. In a further characterization of amethod of producing an outer layer having an entanglement comprising ahydrophobic polymer host and a hydrophilic guest, the steps include:temporarily cloaking at least a portion of the hydrophilic groups of thehydrophilic guest, by performing acylation thereon; entangling the guestand the host by producing a mixture comprising the acylated guest andthe host, and then crosslinking at least a portion of the molecules ofthe guest with the guest. This mixture can then be molded into the outerlayer.

There are many further distinguishing features of the method of theinvention that one will appreciate are associated with the novelfeatures of the outer layer and system of the invention, detailed above.Here, certain of these features are highlighted, once again. In theevent guest complexes are intermingled, the complexes are preferablyselected for their solubility in a cloaking agent solvent—whether thecloaking is performed by silylation or acylation resulting in,respectively, either silylated functional groups or acylated functionalgroups. Acylation may be performed using an acid chloride as anacylating agent, for example. Silylation may be performed usingtrimethylchlorosilane, for example. The crosslinking of guest moleculescan be performed by exposing the cloaked guest within pores of a poroushost structure, to a crosslinker. If the intermingling is performedusing complexes of the guest, the guest complexes may be returned to apre-complex state by dissociation of a group therefrom. Removing thecloaking may include performing a hydrolysis reaction. At least aportion of the crosslinking of the guest may occur during the step ofmolding a mixture of cloaked guest and host; and the step of removingthe cloaking can be performed prior to this step of molding. Asexplained above, entangling may be performed using complexes of a guestrepresented according to the expression HA⁻-QN⁺, where HA representshyaluronic acid and QN⁺ represents a cation. The layer may be thermallyformed into a preselected shape. A system can be produced to include thelayer laminated, or otherwise structurally incorporated onto a structurecomprising the hydrophobic polymer material of the host, forming apreselected form.

Advantages of the invention include, among others: improved mechanicalproperties, such as improved stiffness, modulus, yield stress andstrength; the diffusion profile of the IPN, with its gradualconcentration of guest from the bearing outer surface a depth, d,(generally greater than 100 A and on the order of 100's of microns)provides structural integrity of the bearing surface and its associatedstructure by removing the sharp change in modulus inherent insuperficially coating or grafting a surface according to knowntechniques—thus, making the bearing structure of the invention much lessprone to delamination, while reducing surface friction and wear over thebearing surface.

BRIEF DESCRIPTION OF THE DRAWINGS AND ATTACHMENT A

For purposes of illustrating the innovative nature plus the flexibilityof design and versatility of the preferred outer layer, system andmethod disclosed hereby, the invention will be better appreciated byreviewing the accompanying drawings (in which like numerals, ifincluded, designate like parts) as well as ATTACHMENT A. One canappreciate the many features that distinguish the instant invention fromknown structures and fabrication techniques. The drawings have beenincluded to communicate the features of the innovative outer layer,system and associated method of producing according to the invention byway of example, only, and are in no way intended to unduly limit thedisclosure hereof.

FIG. 1 is a partial, enlarged, cross-sectional view of a system of theinvention (at 10) having a base 18 and outer layer 17.

FIG. 2 is a partial, enlarged, cross-sectional view of a system (at 20)having a base 28 and outer layer 24 produced according to the invention.

FIGS. 3A-3D are depictions of various molecular structures shown here,once again by way of example, as representative structures thereof.

FIG. 4 is a flow diagram depicting details of a method 40 of producingan outer layer having an entanglement according to theinvention—illustrated are core, as well as further distinguishing,features of the invention employing features such as those representedand depicted in FIGS. 1-2 and 3A-3D.

ATTACHMENT A, a twenty-eight page manuscript authored by the applicantsentitled: “IPN Surface Modification of Ultra High Molecular WeightPolyethylene for Lowering Friction and Wear in Total Joint Replacement”is included herewith for its technical background, analysis and supportof the system, outer layer, and method of the invention, and is herebyincorporated herein by reference to the extent necessary to aid infurther understanding the mathematical and rigorous engineering analysesperformed by the applicants in support of their invention

DETAILED DESCRIPTION OF THE DRAWINGS

The partial, enlarged, cross-sectional view of a system 10 in FIG. 1depicts, in a schematic fashion, a base 18 and an outer layer 17. Whilethe outer surface 12 is depicted as planar it is by no means limitedthereto; and rather, the hydrophilic surface 12 is likely, dependingupon application, to have some curvature or slope as depicted andlabeled 22 in the enlarged sectional view of system 20 in FIG. 2. Theouter layer 17 (or 24 in FIG. 2) has an entanglement identified aboveand throughout, of a hydrophobic host and a hydrophilic guest material.Referring, also, to the method depicted in FIG. 4 (box 42), theentanglement preferably comprises an intermingling of cloakedhydrophilic guest and a hydrophobic polymer host, wherein molecules ofthe guest have been crosslinked with each other. The hydrophilic guestof the entanglement may comprise a compound selected from a specifiedgroup consisting of polyions, polysaccharides (including theglycosaminoglycan, hyaluronic acid), salts of glycosaminoglycans,nucleic acids, polyvinylpyrrolidones, peptides, polypeptides, proteins,lipoproteins, polyamides, polyamines, polyhydroxy polymers, polycarboxypolymers, phosphorylated derivatives of carbohydrates, sulfonatedderivatives of carbohydrates, interleukin-2, interferon, andphosphorothioate oligomers, with-or-without amino acids, as well asother hydrophilic polymers. As further identified: polyhydroxy polymersinclude, among others, polyvinyl alcohol and polyethylene glycol; andpolycarboxy polymers include, among others, carboxymethylcellulose,alginic acid, sodium alginate, and calcium alginate.

The intermingling of the guest (box 50, FIG. 4) and host includes aphysical tangling, whether it also comprises crosslinking by primarybonding (chemical/covalent bonding) there-between. Depending upon thetype of intermingling employed, the guest selected for interminglingwith the host, the type of crosslinking of the guest (by chemicalcrosslinking or by way of thermal, ultra-violet “UV”, or other suitableenergy source), as well as composition and form of the host (e.g.,fully- or partially-consolidated porous structure, in powdered form, insolution, and so on), cloaking (box 46 in FIG. 4) may be by any waysuitable, such as by way of performing silylation or acylation, of theguest—making it more hydrophobic. Under certain circumstances, usingcomplexes of the guest may be desirable or even necessary (box 44, FIG.4)—especially where the guest is not sufficiently hydrophobic to undergothe selected cloaking technique. The cloaked groups are then returned toan initial hydrophilic state (box 54, FIG. 4) to produce a generallyhydrophilic outer surface of the layer, this can be by performing ahydrolysis reaction.

As depicted in FIGS. 1 and 2, a base (18 or 28) with which an outerlayer of the invention is inter-linked by suitable means (depending uponfinal application and the environment in which the system will be placedfor operation), is likely comprised of host material. At 16 in FIG. 1, atransition section of the outer layer which, as represented, may includea slightly different consistency or density of intermingled host andguest, or might include an adhesive or film or other means used forinter-connecting/inter-linking the outer layer with a base comprisingthe host material.

For purposes of a more-thorough understanding of the invention and therepresentative examples discussed throughout, FIGS. 3A-3D depict variousmolecular structures employed in connection with producing an outerlayer according to the invention. As shown: the chemical formula for(plain) hyaluronic acid (HA) at 30 in FIG. 3A; in FIG. 3B the formulafor cetyltrimethylammonium bromide 32, as is the structure of the saltcetylpyridinium chloride monohydrate 34; in FIG. 3C the guest complexrepresented by the expression HA⁻-QN⁺, where HA represents hyaluronicacid and QN⁺ represents a cation; and in FIG. 3D a silylated HA⁻-QN⁺complex is depicted. As one can appreciate, the cloaking of HA⁻- QN⁺complexes results in the to hydrophilic groups being replace withsilylated functional groups: hydrogen (H) has been replace withSi(CH₃)₃.

As used herein, for reference, the following acronyms are identified aslisted:

BSA—N, O-Bis(trimethylsilyl)acetamide, a silylation agent.

DMF—N, N-Dimethyl formamide

DMSO—Dimethyl sulphoxide

HA—Hyaluronic acid

HA-CPC—the complex of HA polyannion and cetylpyridinium salt.

HA-CTAB—the complex of HA polyannion and cetyltrimethylammonium salt.

HA⁻-QN⁺—the complex of HA polyannion and long-chain paraffin ammoniumcation.

HMDS—hexamethyldisilazane, a silylation agent.

THF—Tetrahydrofuran

TMCS—trimethylchlorosilane, a silylation agent.

QN⁺—long-chain paraffin ammonium cation.

The flow diagram in FIG. 4 depicts details of a method 40 of producingan outer layer having an entanglement according to theinvention—illustrated are core, as well as further distinguishing,features of the invention employing features such as those representedand depicted in FIGS. 1-2 and 3A-3D. Steps of the method include asshown: Temporarily cloaking (silylation, acylation, etc.) at least aportion of the hydrophilic groups of the guest (46); intermingling atleast a portion of the cloaked guest with the porous polymeric structureby diffusing the cloaked guest into at least a portion of thestructure's pores (50); within the pores, crosslinking at least aportion of the molecules of the guest with the guest (52); and thenremoving the cloaking (54) to produce a generally hydrophilic outersurface of the outer layer. Alternatively, entangling (50, 52) of theguest and the host can be by (a) producing a mixture comprising thecloaked guest and the host, and (b) crosslinking at least a portion ofthe molecules of the guest with the guest. This mixture can then bemolded into the outer layer (58, 59 a/59 b). In the event theintermingling is done with the cloaked guest in powdered form (by, forexample, vacuuming drying washed acylated guest 48) and the host inpowdered form, once the cloaked groups have been returned to an initialhydrophilic state (54), once again, the outer layer may be produced byway of a thermal molding of the powdered form of the guest with the host(reference 58, 59 a).

An IPN is an intimate combination of at least two polymers; it is amaterial network where at least two polymer components are physicallyassociated by being covalently linked. In general, in an IPN, at leastone component is synthesized or cross-linked in the presence of theother, although the two components may or may not be bound together. Itis intended that semi-IPNs fall within the category of IPNs.

Polymeric materials are used in numerous biomedical applications.Polymers characteristically have smooth resilient surfaces. Ultra highmolecular weight polyethylene (UHMWPE) is a biologically inert polymericmaterial that has long been used in total joint replacement(arthroplasty). Despite its many positive attributes such asbiologically compatible and durable, the repetitive motion betweenmating surfaces as in a joint leads to the formation of UHMWPE weardebris. The presence of the wear debris is a negative outcome in alltypes of joints especially an arthroplasty where it can lead to jointloosening and failure of the total joint. The tradeoff to using UHMWPEfor its superior mechanical strength and desirable modulus for bearingweight and repetitive use, is that it is extremely difficult, and somehave considered impossible according to conventional practices, toproduce an IPN using a very hydrophobic polymer such as UHMWPE and avery hydrophilic polymer such as HA. Though considerable effort has beenspent by others to improve the wear resistance of UHMWPE in biomedicalapplications, including topical treatment to decrease the hydrophobicnature of the UHMWPE surface (such as dip-coating or grafting), theseefforts have produced UHMWPE medical device/implants in need of greatersurface lubricity (especially near joint areas) along with sufficientstructural integrity for extended wear in repetitive use applications.Applicants' approach is the synthesis of a new IPN to exploit desirablecharacteristics of UHMWPE and a hydrophilic polymer, leading to asystem/device having increased lubricity and reduced friction and wear.

The step of diffusing according to the invention can include suitabletechniques such as: employing a solvent carrier (including a supercritical fluid such as CO₂) or mixtures of solvents that swell the hostallowing for diffusion of the hydrophilic guest into its host; treatmentof the solvent or a mixture of solvents to make the guest sufficientlyampiphilic for diffusion into the hydrophobic host (e.g., using an HAester); or simultaneous synthesis of host with a guest having a solventcarrier or having been otherwise treated (e.g., thermally molding UHWMPEin the presence of HA treated to make it temporarily hydrophobic toprevent phase separation then cross-linking simultaneously). For furtherdetails of novel diffusion techniques, see ATTACHMENT A. A diffusionprofile of the IPN, with its gradual concentration of guest from thebearing outer surface a depth, d, provides structural integrity of thebearing surface and its associated structure by removing the sharpchange in modulus inherent in superficially coating or grafting asurface according to known techniques. Cross-linking to finally producethe IPN can be done by employing chemical techniques such as that usedby the applicants in earlier work (see that reference above describingthe synthesis of a sequential IPN of an UHMWPE host polymer andpoly-L-lysine (PLL) guest using silylation), or done employing atechnique using another form of energy such as thermal energy orirradiation using a higher-energy source such as UV (ultraviolet)radiation.

If it is an object to produce an outer layer comprised of anentanglement of host and hydrophilic polymer guest creating abio-compatible bearing surface exhibiting lubricity, one can fabricatesuch a bearing structure comprising a hydrophobic host (such as UHMWPE)and a hydrophilic polymer guest (such as hyaluronic acid, HA, or otherpolyion). By way of example, the layer can be synthesized by, first,diffusing the hydrophilic guest (HA) into the hydrophobic host wherebythe hydrophilic guest is temporarily made sufficiently hydrophobic togenerally prevent phase separation thereof until being cross-linked,thus creating the entanglement. The background materials labeledATTACHMENT A may be of further guidance: the guest diffuses into thesurface of the host creating a diffusion profile extending a depth, d,from the bearing outer surface, throughout which a concentrationgradient of cross-linked guest entangled within polymer host is created.The cloaking of the hydrophilic groups of the guest by silylation alongwith a swelling of the host, provides ‘room’ within the host for theguest to diffuse into the host so the guest can be cross-linked withitself, into place. As explained, cloaking groups are then removed byhydrolysis to return the guest to its hydrophilic nature.

Cross-linking to produce the entanglement can be done by employingchemical techniques (e.g., as done in the earlier synthesis by theapplicants of a sequential IPN of an UHMWPE and poly-L-lysine (PLL)guest using silyaltion), or done employing a technique using anotherform of energy such as thermal energy or irradiation using ahigher-energy source such as UV (ultraviolet) radiation.

Hyaluronic acid (HA) is a polysaccharide native to synovial fluid,capable of being crosslinked and possesses exceedingly lubricious, andvery hydrophilic characteristics. The quick biodegradation of HA(hydrolytic and enzymatic) severely limits its application and use as awear or friction surface where higher-stresses are experienced,including bearing structures used in: biomedical applications as jointreplacements, tissue-joint pads, or other implants; sensitive aqueousenvironments such as drinking/potable water facilities; andfood-preparation or pharmaceutical manufacturing equipment (wheretoxicity is a concern).

EXAMPLE 1

The following technical discussion is presented by way of example, only,and concerns the synthesis of an entanglement, such as an IPN, intobearing structures according to the invention (see, also, detailedtechnical discussion found in ATTACHMENT A):

A. Silylation of HA: The hydroxyl and acetamido groups in HA must besilylated to make them more hydrophobic so that the HA will dissolve ina solvent which swells

UHMWPE. Preferred criteria for the silylation agent are: (1) effectivelysilylate the HA without complex reaction conditions; (2) should notproduce insoluble byproducts so that the reaction product is easilypurified; (3) the bonding between Si and 0 strong enough to resistcleavage by moisture in air during silylation and swelling, and weakenough so that it can hydrolyze under certain conditions (allowingreturn of HA to hydrophilic state after the synthesis is complete).

The following silylation agents will be measured against the abovecriteria: N, O-bis(trimethylsilyl)acetamide (BSA),bis(trimethylsilyl)trifluoroacetamide (BSTFA), trimethylchlorosilane(TMCS), and ethyldimethylchlorosilane. The reaction conditions may bethose used with the PLL silylation procedures according to applicantsprior work, although preferably reaction temperatures will be kept aslow as possible (<50° C.) to avoid HA thermal degradation. The reactionproducts of the silylation agents are the formation of trimethylsilylethers, which are extremely prone to hydrolysis. Preferably, the IPN issynthesized without air.

B. Solvent and Crosslinking Agent Selection: Earlier, the applicants'identified that xylenes yield the highest degree of swelling of UHMWPE.Xylenes will be the solvent used for the IPN synthesis in this example.Methylene chloride and 1,1,1-trichloroethane swell UHMWPE almost as wellas xylenes. Thus, each of these solvents will be tried (xylenes,Methylene chloride, and 1,1,1-trichloroethane) to solvate the silylatedHA and crosslinker.

The crosslinker criteria include: (1) the crosslinkers are preferablysoluble in the solvent used, whether xylenes, methylene chloride or1,1,1-trichloroethane; (2) the crosslinking reaction preferably occursbetween the hydroxyl groups of HA, leaving the carboxyl groups alone forrecruiting synovial fluid to decrease friction; and (3) the crosslinkedHA is preferably stable in the physiological environment in whichbearing structure is used. Glutaraldehyde (GA) and di- orpoly-isocyanates are crosslinker candidates. Known uses ofglutaraldehyde include use in the crosslinking of proteins such ascollagen. GA not only interacts with amino groups (as it is commonlyused), but can also react with hydroxyl groups of polysaccharide inaqueous solution or organic solvent such xylene under acidic conditions.The aldehyde groups of GA presumably react with the hydroxyl groups ofHA to produce hemiacetalization or full acetalization. Regarding the useof di-isocyanates to crosslink HA coatings: The polysaccharide moleculesare covalently bonded by periodic urethane links.

C. Ex situ Crosslinking: To verify that HA can be crosslinked by theselected crosslinker in the swelling solvent, and to determine theeffect of trimethylsilyl or ethyldimethysilyl groups on thecrosslinking, one can perform ex situ crosslinking and examine thecrosslinked products. Here, silylated HA will be dried and solvated withthe selected solvents, and then be transferred to a glass tubecontaining the crosslinker. Crosslinked gels will be allowed to reactuntil several hours after the last visual change. After the gels havedried, water is added to cause hydrolysis and liberate of thetrimethylsilyl or ethyldimethysilyl groups. Preferably, an investigationof various crosslinking concentrations is done so that swelling ratiosof the formed gels can be compared to assess the degree of crosslinkingfor each concentration.

D. IPN Synthesis: IPN synthesis is performed using the solvent,silylation agent, and crosslinker selected. The swell times and swellingtemperatures will be chosen based on what the HA can withstand. While HAis extremely susceptible to thermal degradation in the presence ofwater, once silylated and dissolved in an air-free organic solvent itmay withstand higher temperatures. Of interest are the temperatures atwhich silylation, swelling and crosslinking occur; to assess, one canlook to how much the viscosity of the HA solutions decrease at varioustemperatures. It is anticipated that only during silylation will thetemperatures have to be kept below 50° C., but during the other portionsof the synthesis temperatures of 50-70° C. may be acceptable.

For reference purposes, the following additional definitions areoffered: “Ophthalmic lenses” refers to contact lenses (hard or soft),intraocular lenses, eye bandages and artificial corneas, lenses may beplaced in intimate contact with the eye or tear fluid, such as contactlenses for vision correction. “Hydrophilic”, as used herein, describes amaterial or portion thereof which will more readily associate with waterthan with lipids. A “hydrophilic surface”, as used herein, refers to asurface which is more hydrophilic (i.e., more lipophobic) than the bulkor core material of an article. Thus, an ophthalmic lens having ahydrophilic surface describes a lens having a core material having acertain hydrophilicity surrounded, at least in part, by a surface whichis more hydrophilic than the core. “Polyion” or “polyionic material”, asused herein, refers to a polymeric material including a plurality ofcharged groups, which includes polyelectrolytes, p- and n-type dopedconducting polymers. Polyionic materials include both polycations(having positive charges) and polyanions (having negative charges). A“polymer” is a molecule built up by repetitive chemical union or bondingtogether of two or more smaller units called monomers. Polymer includesoligomers, which have two to about 80 monomers, and polymers having morethan 80 monomers. A polymer can be linear, branched network, star, comb,or ladder types of polymer; polymers may be synthetic,naturally-occurring or semi-synthetic.

A polycation is a polymer containing a net positive charge, for examplepoly-L-lysinc hydrobromide. While a polycation can contain monomer unitsthat are charge positive, charge neutral, or charge negative, however,the net charge of the polymer is positive. A polycation also can mean anon-polymeric molecule that contains two or more positive charges. Apolyanion is a polymer containing a net negative charge, for examplepolyglutamic acid. While a polyanion can contain monomer units that arecharge negative, charge neutral, or charge positive, however, the netcharge on the polymer is negative. A polyanion can also mean anon-polymeric molecule that contains two or more negative charges.“Nucleic acid” refers to a polymer containing at least two nucleotides(which contain a sugar deoxyribose (DNA) or ribose (RNA), a base, and aphosphate group).

UHMWPE is a polyethylene having an estimated weight average molecularweight in excess of about 400,000, usually 1,000,000 to 10,000,000 asdefined by a melt index (ASTM D-1238) of essentially zero and a reducedspecific viscosity greater than 8, preferably 25-30. A porous UHMWPEpreform may be used as the host and/or base material in a system of theinvention that includes an outer layer. Preform, as used here, refers toa shaped article which has been consolidated, such as by ram extrusionor compression molding of UHMWPE resin particles into rods, sheets,blocks, slabs or the like. Preforms may be obtained or machined fromcommercially available UHMWPE, for example GUR 4150 HP ram extrudedUHMWPE rods from PolyHi Solidur (Fort Wayne, Id.). Silane crosslinkedUHMWPE has been used for components of total hip replacements. Othermodifications of UHMWPE, include: reinforcement with carbon fibers; andpost-processing treatments such as solid phase compression molding. Thecrosslinking of polymers may be either non-ionic (e.g., covalent) orionic crosslinking. Ions used to ionically crosslink the polymers arepolyions and may be anions or cations depending on whether the polymeris cationically or anionically crosslinkable.

EXAMPLE 2

By way of further examples the following is offered: In the case ofusing a guest of HA, which is strongly hydrophilic with its many polargroups (—COOH, —OH and —CONHCH₃) on its long molecular chain, diffusionof HA molecules directly into a bulk UHMWPE structure is difficult.Therefore a modification of the HA molecules is done to increasehydrophobicity and compatibility with both UHMWPE and organic solventsused in connection with cloaking.

2A) Silylation of HA to increase its hydrophobicity: Silylation is aknown technique for increasing hydrophobicity, and createorganic-solublederivatives of substances. During a silylation reaction of HA, thehydrophilic groups containing active hydrogen, such as —COOH, —OH, and—NH₂, are masked by hydrophilic silyl groups. The reaction isreversible, the silylated functional groups can be returned to theiroriginal state through hydrolysis reaction. HA is a muco-polysaccharideof molecular weight up to millions (˜10⁶). Compared with silylation ofpoly-L-lysine (MW=˜1000), silylating HA is difficult due to its largemolecular weight. In contrast to PLL silylation previously performed bythe applicants (see above), preferably HA is modified before silylationto increase its solubility in silylation solvents (polar organicsolvents can be used). The steps include:

(1) Reaction of HA with long-chain aliphatic quaternary ammonium salts(QN⁺). Polyanions, such as HA, combined with certain organic cations,such as paraffin chain ammonium (QN⁺) ions, produces a precipitablecomplex. The complex is a true salt of the polyacid and quaternary base.HA was modified with long-chain aliphatic ammonium salts, to improve itssolubility in organic solvents. Combination of QN+ with polyannionsoccurs in those pH ranges in which the polyannions are negativelycharged. The reaction between HA and ammonium cations in water can beexpressed:

HA⁻Na⁺+QN⁺A⁻→HA⁻-QN⁺↓+Na⁺A⁻

where HA⁻-Na⁺ is the sodium salt of hyaluronic acid; HA⁻-QN⁺ is theprecipitable complex between HA carboxylic polyanion and long chainparaffin ammonium cations. HA⁻-QN⁺ (HA-CPC/HA-CTAB) complexes were used.The complexes (HA⁻-QN⁺) precipitated from HA aqueous solution aresoluble in concentrated salt solutions, so HA can be recovered from itsinsoluble complexes. Ammonium salts used were: cetyltrimethylammoniumbromide monohydrate (MW: 358.01) (CTAB) and cetylpyridinum chloride(M.W. 364.46) (CPC).

(2) Silylation of HA⁻-QN⁺ complexes: HA-CPC and HA-CTAB were silylatedin DMSO solution with BSA, HMDS and other typical silylation agents.Silylation agents are generally sensitive to humidity, silylatingoperation should be under the purge of dry N₂.

2B) Acylation of HA to improve its thermal flow: To make HA flowable athigh temperature, the strong hydrogen bonding between its molecules mustbe disrupted, and the molecular order (i.e., crystallinity) of HA needsto be destroyed. Acylating the hydroxyl groups on HA with long-chainaliphatic carboxylic acids chloride will help in de-crystallizing HA.Acid chlorides, from caproyl to stearoyl chloride, can be used asacylating agents. Acylation is a known process for disruptingcrystallinity in other polysaccharides. Acylation reactions areperformed in solution (of HA⁻-QN⁺ in DMSO, for example). Start with aDMSO solution of HA⁻-QN⁺ complex using the technique described above inconnection with Silylation of HA, above. Acylation is done to make thehydrophilic guest hydrophobic enough to be molded with a hydrophobichost, such as UHMWPE, without phase separation.

2C) Entanglement by Swelling of Host to Facilitate Diffusion of Guest:(a) Swell UHMWPE bulk samples from bar stock or molding in an xylenesolution of silylated HA⁻-QN⁺ complex. The swelling may be performed at70° C. for about two weeks. The micro-voids created with swelling in theamorphous region of UHMWPE will allow silylated HA⁻-QN⁺ complex todiffuse in. (b) Crosslink the silylated HA⁻-QN⁺ molecules that havediffused into UHMWPE in situ with di-/poly-isocyanate, such as1,8-diisocyanatooctane. The reaction was performed in isocyanate xylenesolution. (c) Deswell the samples to remove the xylenes residues. (d)Remove the trimethylsily groups with hydrolysis to recover thehydrophillic —OH and CH₃COONH— groups. (e) Remove the long-chainparaffin ammonium ions (QN⁺) in concentrated salt solution to recover—COOH groups. QN⁺ will dissociate from —COO⁻ groups on HA inconcentrated salt solution, such as NaCl, KCl, NaSO₄, etc. Several 0.4NNaCl washings may be necessary for sufficient removal of QN⁺.

2D) Entanglement by using Porous (e.g., UHMWPE) Host Structure: (a) MoldUHMWPE powders to produce a preform with controlled porous density (poresize about 20 microns, porosity around 30%). (b) Soak the preform withxylene solution of silylated HA-QN⁺ complex (e.g., approx. one hour).The pores, whether interconnected, allow HA molecules to diffuse intoUHMWPE. (c) Crosslink the HA-QN⁺ inside UHMWPE preform with anappropriate crosslinker such as, but not limited to, adi-/polyisocyanate. Note: select a solvent that will not solvate thesilylated HA-QN+. (d) May perform a ‘light’ molding (do not mold tofully dense) to aid in physically trapping the HA guest inside theUHMWPE porous structure. (e) Recover —COON, —OH and CH₃COONH— groups onHA. (f) (Re)mold and size the treated preform to final shape—keeptemperature below that which will degrade HA.

2E) Entanglement by Powdered Mixture which can be Molded: HA can formentanglement with UHMWPE during the procedure of molding their powdermixture.

The strong hydrophibicity from acylation of HA aids in making HAcompatible with UHMWPE so that phase separation does not occur. (a) MoldUHMWPE bulk under the standard molding cycles into a slightly undersizedbase structure depending upon application of resulting device. (b) Onthe surface of this undersized molded bulk UHMWPE device/object, put athin layer of powered HA-crosslinker-UHMWPE mixture (preferably cloakedusing acylation—see above 2B), and then mold it to a selected shape andsize. (c) Recover the hydrophillic functional groups on HA.

While certain representative embodiments and details of an EXAMPLE havebeen shown merely for the purpose of illustrating the bearing structuresand associated technique of synthesizing IPN, those skilled in the artwill readily appreciated the various modifications may be made to theserepresentative embodiments without departing from the novel teachings orscope of this technical disclosure. Accordingly, all such modificationsare intended to be included within the scope of this invention asdefined in any illustrative-claim included below. Although the commonlyemployed preamble phrase “comprising the steps of” may be used herein,or hereafter, in a method claim, the Applicants do not intend to invoke35 U.S.C. Section 112 §6. Furthermore, in any claim that is filedherewith or hereafter, any means-plus-function clauses used, or laterfound to be present, are intended to cover at least all structure(s)described herein as performing the recited function and not onlystructural equivalents but also equivalent structures.

1-6. (canceled)
 7. A system comprising an outer layer having anentanglement comprising a hydrophobic polymer host and a hydrophilicguest, said outer layer being formed into a structure comprising a basecomprising the hydrophobic polymer of the host; wherein the hydrophilicguest comprises a compound selected from the group consisting ofpolyions, polysaccharides, salts of glycosaminoglycans, nucleic acids,polyvinylpyrrolidones, peptides, polypeptides, proteins, lipoproteins,polyamides, polyamines, polyhydroxy polymers, polycarboxy polymers,phosphorylated derivatives of carbohydrates, sulfonated derivatives ofcarbohydrates, interleukin-2, interferon, and phosphorothioateoligomers; the entanglement comprises an intermingling of cloakedhydrophilic groups of the hydrophilic guest with the hydrophobic polymerhost, and crosslinked molecules of the hydrophilic guest with the guestand said cloaked groups having been returned to an initial hydrophilicstate to produce a generally hydrophilic outer surface of the layer, andwherein said generally hydrophilic outer surface of the layer isselected from the group consisting of: a bearing surface; a flexiblebarrier surface separating a first and second area; a transparent membersurface; an in vivo implant surface; a drag reduction surface; areaction resin surface; a topical dressing surface; and a dental splintsurface.
 8. An outer layer having an entanglement comprising ahydrophobic porous polymeric host structure and a hydrophilic guest,comprising: the hydrophilic guest comprises a compound selected from thegroup consisting of polyions, polysaccharides, salts ofglycosaminoglycans, nucleic acids, polyvinylpyrrolidones, peptides,polypeptides, amino acids, proteins, lipoproteins, polyamides,polyamines, polyhydroxy polymers, polycarboxy polymers, phosphorylatedderivatives of carbohydrates, sulfonated derivatives of carbohydrates,interleukin-2, interferon, and phosphorothioate oligomers; and theentanglement comprising an intermingling of cloaked hydrophilic groupsof the hydrophilic guest diffused into a plurality of pores of theporous polymeric host structure, and crosslinked molecules of thehydrophilic guest with the guest; and said cloaked groups having beenreturned to an initial hydrophilic state to produce a generallyhydrophilic outer surface of the layer.
 9. An outer layer having anentanglement comprising a hydrophobic polymer host and a hydrophilicguest, comprising: the hydrophilic guest comprises a compound selectedfrom the group consisting of polyions, polysaccharides, salts ofglycosaminoglycans, nucleic acids, polyvinylpyrrolidones, peptides,polypeptides, amino acids, proteins, lipoproteins, polyamides,polyamines, polyhydroxy polymers, polycarboxy polymers, phosphorylatedderivatives of carbohydrates, sulfonated derivatives of carbohydrates,interleukin-2, interferon, and phosphorothioate oligomers; and theentanglement comprises an intermingling of acylated hydrophilic groupsof the hydrophilic guest in a powdered form with a powdered form of thehost, and crosslinked molecules of the hydrophilic guest with the guest;said acylated groups having been returned to an initial hydrophilicstate to produce a generally hydrophilic outer surface of the layer; andthe layer produced by way of a thermal molding of said powdered form ofthe guest with the host.
 10. A method of producing an outer layer havingan entanglement comprising a hydrophobic porous polymeric structure anda hydrophilic guest, the method comprising the steps of: temporarilycloaking at least a portion of the hydrophilic groups of the guest;intermingling at least a portion of said cloaked guest with the porouspolymeric structure by diffusing the cloaked guest into at least aportion of the structure's pores; within said pores, crosslinking atleast a portion of the molecules of the guest with the guest; andremoving said cloaking to produce a generally hydrophilic outer surfaceof the outer layer.
 11. The method of claim 10 wherein: the guest is apolysaccharide; said intermingling is performed using complexes of theguest comprising an QN⁺ group, where QN⁺ represents a long-chainparaffin ammonium cation; said cloaking said hydrophilic groups of saidcomplexes comprises performing a silylation using a silylating agent;and said step of removing further comprises performing a hydrolysisreaction.
 12. The method of claim 10 wherein: the hydrophobic porouspolymeric structure is a molded form comprising ultra high molecularweight polyethylene; said polysaccharide is hyaluronic acid; saidintermingling is performed using complexes of the guest comprising anQN⁺ group, where QN⁺ represents a cation selected from the groupconsisting of alkyltrimethylammonium chloride, alkylamine hydrochloride,alkylpyridinium chloride, alkyldimethylbenzyl ammonium chloride,alkyltrimethylammonium bromide, alkylamine hydrobromide, alkylpyridiniumbromide, and alkyldimethylbenzyl ammonium bromide; and furthercomprising the step of dissociating said QN⁺ groups from said guestcomplexes in a salt solution.
 13. The method of claim 10 wherein: theguest comprises a compound selected from the group consisting ofpolyions, polysaccharides, salts of glycosaminoglycans, nucleic acids,polyvinylpyrrolidones, peptides, polypeptides, amino acids, proteins,lipoproteins, polyamides, polyamines, polyhydroxy polymers, polycarboxypolymers, phosphorylated derivatives of carbohydrates, sulfonatedderivatives of carbohydrates, interleukin-2, interferon, andphosphorothioate oligomers; said cloaking said hydrophilic groupscomprises performing a silylation using a silylating agent; and saidcrosslinking further comprises exposing said cloaked guest within saidpores to a crosslinker; and further comprising the step of thermallyforming the layer into a preselected shape.
 14. The method of claim 13wherein: said polyhydroxy polymers comprise a polymer selected from thegroup consisting of polyvinyl alcohol and polyethylene glycol; saidpolycarboxy polymers comprise a polymer selected from the groupconsisting of carboxymethylcellulose, alginic acid, sodium alginate, andcalcium alginate; said intermingling is performed using complexes of theguest; and said step of removing further comprises performing ahydrolysis reaction; and further comprising the step of returning theguest complexes to a pre-complex state by dissociation of a grouptherefrom.
 15. A system comprising the layer produced according to themethod of claim 10 thermally-formed with a base comprising thehydrophobic porous polymer of the structure into a preselected form; andwherein said generally hydrophilic outer surface of the layer isselected from the group consisting of: a bearing surface; a flexiblebarrier surface separating a first and second area; a transparent membersurface; an in vivo implant surface; a drag reduction surface; areaction resin surface; a topical dressing surface; and a dental splintsurface.
 16. A method of producing an outer layer having an entanglementcomprising a hydrophobic polymer host and a hydrophilic guest,comprising the steps of: temporarily cloaking at least a portion of thehydrophilic groups of the hydrophilic guest, by performing acylationthereon; entangling the guest and the host by producing a mixturecomprising said acylated guest and the host, and crosslinking at least aportion of the molecules of the guest with the guest; and molding saidmixture into the outer layer.
 17. The method of claim 16 wherein theguest comprises a compound selected from the group consisting ofpolyions, polysaccharides, salts of glycosaminoglycans, nucleic acids,polyvinylpyrrolidones, peptides, polypeptides, amino acids, proteins,lipoproteins, polyamides, polyamines, polyhydroxy polymers, polycarboxypolymers, phosphorylated derivatives of carbohydrates, sulfonatedderivatives of carbohydrates, interleukin-2, interferon, andphosphorothioate oligomers; and further comprising the steps of dryingsaid acylated guest complexes, said mixture is in powdered form, andfurther comprising the step of removing said cloaking to produce agenerally hydrophilic outer surface of the outer layer.
 18. The methodof claim 17 wherein: the guest is a polysaccharide; said entangling isperformed using complexes of the guest comprising an QN³⁰ group, whereQN⁺ represents a long-chain paraffin ammonium cation; said performingacylation further comprises using an acid chloride; and said removingfurther comprises performing a hydrolysis reaction.
 19. The method ofclaim 16 wherein: the guest is hyaluronic acid; said entangling isperformed using complexes of the guest represented according to theexpression HA⁻-QN⁺, where HA represents hyaluronic acid and QN⁺represents a cation; said cloaked hydrophilic groups of the guestcomplexes comprise acylated functional groups; and at least a portion ofsaid crosslinking to occur during said step of molding said mixture; andfurther comprising, prior to said step of molding, the step of removingsaid cloaking to produce a generally hydrophilic outer surface of theouter layer.
 20. A system comprising the layer produced according to themethod of claim 16 laminated onto a structure comprising the hydrophobicpolymer material of the host, forming a preselected form.
 21. The systemof claim 19 wherein said cloaking is removed to produce a generallyhydrophilic outer surface of the outer layer, and said outer surface isselected from the group consisting of: a bearing surface; a flexiblebarrier surface separating a first and second area; a transparent membersurface; an in vivo implant surface; a drag reduction surface; areaction resin surface; a topical dressing surface; and a dental splintsurface.